MANIPULATION OF SUBSTRATE UTILIZATION WITH SOMATOSTATIN IN PATIENTS WITH SECONDARY MULTIPLE ORGAN DYSFUNCTION SYNDROME

Objectives: To determine whether glucose utilization and metabolic substrate (glucose and fat) oxidation could be manipulated in patients with secondary multiple organ dysfunction syndrome. Design: Prospective study. Setting: Intensive care units (ICU) of two university hospitals. Patients: Eight adults free of hepatic disease and hemodynamically stable at the time of study, but with failed respiratory and gastrointestinal systems, who thus required mechanical ventilation and intravenous nutrition. Interventions: Patients were infused with 20% dextrose through central venous cannulas at rates that increased and maintained (clamped) their plasma glucose concentration at 216 mg/dL, (12 mmol/L) for 3 hrs. Somatostatin was infused continuously during the second and third hours of the clamp to reduce plasma concentrations of endogenous insulin and glucagon, Exogenous insulin was administered together with somatostatin during the third hour to restore basal insulin concentrations. Energy expenditure was measured by indirect calorimetry throughout the study and blood samples were withdrawn regularly for determination of metabolite and hormone concentrations. Main statistical comparisons were made between the baseline data (first hour of the study) and data collected during the second and third hours of the clamp. Measurements and Main Results: Plasma glucagon concentrations were reduced by nearly 50% (p < .05) toward the end of the study, whereas no significant changes in plasma concentrations of cortisol or growth hormone occurred. Energy expenditure did not change significantly at any time during the clamp procedure. Glucose utilization (6.1 mg/kg/min [34 mu mol/kg/min]) during the first hour of the hyperglycemic clamp, decreased by 53% (p < .05) with the infusion of somatostatin during the second hour of the clamp. However, once exogenous insulin was infused during the third hour, glucose utilization increased by 55% (p < .05) when compared with the baseline (hour 1) rate. Glucose oxidation was nearly doubled during the third hour of the study when compared with oxidation rates during the first and second hours. Fat oxidation decreased steadily during the 3-hr clamp. Conclusions: Glucagon has a significant inhibitory effect on glucose utilization during intravenous glucose infusion in the multiple organ dysfunction syndrome patient. Pharmacologic intervention with somatostatin and insulin (physiologic dose) can facilitate glucose utilization and oxidation in these patients. Further investigations are needed to determine whether long-term alteration of glucose and fat metabolism would be beneficial in the patient with secondary multiple organ dysfunction syndrome.